|Year : 2020 | Volume
| Issue : 2 | Page : 84-87
A rare case of Brooke–Spiegler syndrome
Anuja Sunkwad1, Sunanda Mahajan1, Jayati Dave1, Dhanjit Kumar Das2
1 Department of Dermatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Scientist-E, Genetic Research Centre, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
|Date of Submission||11-Feb-2020|
|Date of Decision||10-Jun-2020|
|Date of Acceptance||28-Jun-2020|
|Date of Web Publication||22-Dec-2020|
Dr. Sunanda Mahajan
Department of Dermatology, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant inherited disorder characterized by multiple skin appendageal tumors. The predominant tumors can be a cylindroma, trichoepithelioma, and/or spiradenoma. Here we report this rare entity of Brooke–Spiegler syndrome in a 50 year old female on the basis of clinico-histopathological correlation. The gene responsible for this condition is cylindromatosis gene (CYLD1) which has been mapped on chromosome 16q12–q13. However, no mutation have been detected in CYLD gene analyzed in our patient which indicates lack of genotype–phenotype correlation in this patient.
Keywords: Brooke–Spiegler syndrome, cylindromatosis gene, cylindroma, spiradenoma, trichoepithelioma
|How to cite this article:|
Sunkwad A, Mahajan S, Dave J, Das DK. A rare case of Brooke–Spiegler syndrome. Indian J Dermatopathol Diagn Dermatol 2020;7:84-7
|How to cite this URL:|
Sunkwad A, Mahajan S, Dave J, Das DK. A rare case of Brooke–Spiegler syndrome. Indian J Dermatopathol Diagn Dermatol [serial online] 2020 [cited 2021 Jun 19];7:84-7. Available from: https://www.ijdpdd.com/text.asp?2020/7/2/84/304334
| Introduction|| |
Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant inherited disorder characterized by multiple skin appendageal tumors. The predominant tumors can be cylindroma, trichoepithelioma, and/or spiradenoma.
The locus has been mapped on chromosome 16q12–q13. The gene is known as the cylindromatosis gene (CYLD1) and is a tumor-suppressor gene. Loss-of-function mutation of this gene is believed to increase resistance to apoptosis. Very few cases of BSS are reported in the literature so far. Here, we report this rare entity of BSS on the basis of clinicohistopathological correlation.
| Case Report|| |
A 50-year-old female accompanied by her daughter presented to us with complaints of multiple papulonodular lesions and tumor-like masses of varying sizes over scalp, face, neck, back, and lower extremity since the age of 12 years. The patient described the appearance of initial lesion as multiple, soft, small, pea-sized skin-colored papules over nose and forehead (mid-face involvement). All the lesions were limited to face till the age of 20 years when she noticed sudden bouts of multiple such lesions over scalp, ears, shoulder, back, and lower extremity post her first pregnancy. All the lesions were persistent since then with a history of gradual increase in size over the period of 15–20 years. The patient gave a positive family history of similar looking lesions to her maternal uncle and in three out of four siblings [Chart 1]. Affected family members were not available for examination at our center; however, according to the patient, their presentation was milder and of lesser intensity than hers. Our patient had single living issue who is a 32-year-old healthy female and had no signs of the disease. The patient's general health was good, and all routine investigations were normal. There was no history of childhood seizures or developmental delay. No any visual or auditory impairment was observed in the patient. Apart from this, the patient had generalized weakness and transient syncopal attacks few months ago, for which magnetic resonance imaging of the brain was done which was normal. Contrast tomography of the face with three-dimensional reconstruction showed extensive nodules over forehead, nose, and auricular region [Figure 1]b.
|Figure 1: (a and b) Clinical and computed tomographic image of the face showing “turban appearance” and “cauliflower-like appearance”|
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On examination, there were multiple oval smooth, translucent to skin-colored papules of 2–5 mm in diameter on the mid-face, particularly over nose, chin, and the upper lip with central umbilication [Figure 2]a. Additional multilobulated nodules and masses were seen on the scalp, forehead, and both the pinna, giving it “turban appearance” and “cauliflower-like appearance,” respectively [Figure 1]a and [Figure 2]b. These were dome-shaped, firm, hairless, pink nodules of variable diameter (1.0–5.0 cm) with visible surface telangiectasia. Multiple hard, firm, tender nodules were distributed over midline of the back and lower extremity [Figure 2]c and [Figure 2]d.
|Figure 2: (a-d) Multiple papules, nodules, and tumor-like masses distributed over the face, scalp, pinna, midline of back, and over lower extremity|
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Three different morphological lesions were biopsied. Histopathological examination of a forehead nodule demonstrated a well-defined dermal lesion composed of islands of basaloid cells arranged in a jigsaw puzzle-like pattern [Figure 3]a and [Figure 3]b; this characteristic appearance was suggestive of cylindroma. Histopathology of the chin papule demonstrated branching basaloid aggregations. These basaloid aggregations are composed of small dark basaloid cells along with peripheral palisading and central area of eosinophilic amorphous material. Stromal clefts were absent in between the aggregations suggestive of trichoepithelioma [Figure 4]a and [Figure 4]b. Histopathology of the upper back nodule showed islands of lobules composed of small dark staining basaloid cells peripherally and larger cells with paler nuclei centrally. Lobules are surrounded by condensed connective tissue making diagnosis consistent with spiradenoma [Figure 5]a and [Figure 5]b.
|Figure 3: (a and b) Islands of basaloid cells arranged in a jigsaw puzzlelike pattern, suggestive of cylindroma (H and E, ×10, ×20)|
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|Figure 4:(a and b) Lobules of dark basaloid cells with peripheral pallisading and central area of eosinopholic amorphous material with absent stromal clefts, suggestive of trichoepithelioma (H and E, ×10, ×20)|
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|Figure 5:(a and b) Islands of lobules composed of small dark staining basaloid cells peripherally and larger cells with paler nuclei centrally, suggestive of spiradenoma (H and E, ×4, ×20)|
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Based on the clinical picture, their typical histopathological findings and coexistence of these three appendageal tumors, namely cylindroma, trichoepithelioma, and spiradenoma, lead us to diagnosis of BSS.
Genetic study was carried out on the blood sample. Patients' DNA sample was isolated from the blood. The quality and quantity of genomic DNA were checked by ultraviolet spectrophotometer. The entire gene of CYLD was amplified, and it was subjected for automated DNA sequencing analysis. On analysis of all the DNA sequences, no mutation or genomic variants were identified.
| Discussion|| |
BSS is an autosomal dominantly inherited disease characterized by multiple skin appendageal tumors. The predominating tumor can be cylindroma, trichoepithelioma, and/or spiradenoma. Although cylindromas and spiradenomas are the sweat gland tumors, trichoepitheliomas show hair follicle differentiation., According to Fenske et al., it has been postulated that BSS results from defects in the regulation of putative stem cells of the folliculosebaceous-apocrine unit, giving rise to different skin appendage tumors.
The disease also demonstrated variable clinical and histopathological features among the affected members of a single family, in which older members tend to have larger lesions that are also greater in number as compared to the younger members., This explains larger size lesions in our case who is a 50-year-old female.
The gene for BSS is known as the CYLD1; it is a tumor-suppressor gene. Loss-of-function mutation of this gene is believed to increase resistance to apoptosis. The penetrance of the gene has been estimated to be between 60% and 100%., However, no mutation or genomic variants have been detected in CYLD gene analyzed in our patients' sample. Absence of mutation in this particular gene does not rule out the presence of any other genetic locus. Bowen et al. described three families with BSS, one with familial cylindroma, and two with multiple familial trichoepithelioma, showed phenotypes associated with novel and recurrent mutations in CYLD, and provided evidence that these disorders represent phenotypic variation and also lack of genotype–phenotype correlation.,
Very few cases of BSS around 50 are available in the literature so far. Most of them are reported with cylindromas and trichoepithelioma; whereas, in our case, all the three tumors were present. Although individual lesions are considered to be benign, they should be watched for malignant transformation. We propose complete genetic analysis of such patients and affected family members for further understanding of the disease and research purpose.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]